The extended hippocampal-diencephalic memory system: enriched housing promotes recovery of the flexible use of spatial representations after anterior thalamic lesions.

The anterior thalamic (AT) nuclei constitute an important component of an extended hippocampal-diencephalic system, and severe persisting memory deficits are normally found after AT damage. This study examined whether postoperative enrichment promotes the recovery of the flexible use of spatial representations in rats with AT lesions. After training to swim from a single constant start position to a submerged platform in a Morris water maze, rats with AT lesions that were housed in standard cages (AT-Std) performed poorly when required to swim to the platform from novel start positions during probe trials. By contrast, rats with AT lesions but housed in enriched environments (AT-Enr), like sham-lesion rats, showed relatively little disruption when tested with novel start positions. AT-Std rats also initially showed impaired acquisition of the task, whereas AT-Enr rats learned at a similar rate to that of the Sham-Std group. Beneficial effects of enrichment were replicated in the subsequent standard water maze procedure that used varying start positions throughout training to acquire a new platform location. Although it is clear that AT damage can severely disrupt episodic-like memory processes, and appear to be a core part of the interlinked neural systems subserving episodic memory, the current findings strongly encourage study on the adaptive response of the brain to thalamic lesions and prospects for the development of rehabilitation programs in cases of anterograde amnesia associated with diencephalic injury.

Reflections on the use of the concept of plasticity in neurobiology. Translation and adaptation by Bruno Will, John Dalrymple-Alford, Mathieu Wolff and Jean-Christophe Cassel from J. Paillard, J Psychol 1976;1:33-47.

After having underlined the ambiguities of the concept of plasticity and the dangers of its purely metaphoric use in neurobiology, it is suggested that we return to a more precise definition of the structure, the operating principles and the function of the "systemic" unit or "integron" relevant to the particular level of analysis in question. Any change can then be described as a modification of function, a change in the operation principles, or an alteration of the material structure of the system. It is suggested that the term plastic should be restricted to describing, among the possible variations in the operating principles or the function of a given system, any lasting alteration of the connectivity network of the system under the influence of an external force or environmental constraint. Therefore, systematic or random variations of performance, functional flexibility or the vicarious(1) processes or strategies that can be found in a rigidly wired system are not justified examples of plasticity.

The concept of brain plasticity--Paillard's systemic analysis and emphasis on structure and function (followed by the translation of a seminal paper by Paillard on plasticity).

Although rejected for the most part of the 20th Century, the idea of brain plasticity began to receive wide acceptance from the 1970s. Yet there has been relatively little theoretical comment on the definition and use of "plasticity" in the field of neurobiology. An early exception to this lack of critical reflection on neural plasticity was provided by Jacques Paillard in a seminal paper that he published in 1976 [Paillard J. Réflexions sur l'usage du concept de plasticité en neurobiology. J Psychol 1976;1:33-47]. As this valuable contribution was published in French, the present authors provide an English adaptation to help convey his ideas to an international audience, together with a contemporary commentary on this paper. Paillard's definition of the term "plasticity" is probably as pertinent today as it was 30 years ago, especially in terms of its relevance to multiple levels of analysis of brain function (molecular, cellular, systemic). Sadly, Jacques Paillard died in 2006; our comments therefore also include a brief biographical tribute to this outstanding neuroscientist.

Recovery from brain injury in animals: relative efficacy of environmental enrichment, physical exercise or formal training (1990-2002).

In the 1960s, it was shown for the first time that enriched housing enhances functional recovery after brain damage. During the 1970s and 1980s, many findings similar to this initial one have been reported, enlarging greatly its generality. Over the last 13 years, many different kinds of brain damage were modelled in animals or even directly studied in humans. Overall, these recent studies corroborated earlier findings, although occasional exceptions were reported. Other critical data, obtained mainly in intact animals, showed that enriched housing increases neurogenesis in the adult hippocampus. Recent evidence that this neurogenesis is involved in hippocampal-dependent learning supports the original interpretation of the enrichment effects as being the result of an accumulation of informal learning experiences (e.g., [. Heredity, environment, brain biochemistry, and learning. In: Current Trends in Psychological Theory. University of Pittsburgh Press, Pittsburgh, pp. 87-110;. Brain changes in response to experience. Sci. Am. 226, 22-29]). Other components of enriched environment, such as physical exercise, may have additive effects with those of training. The comparison of the relative effectiveness of enriched experience, of physical exercise and of training on structural and/or functional assessments of recovery, shows that training/learning is generally more effective than physical exercise and that enriched experience is a more potent therapy than either of these two other treatments. The combination of enriched experience with some other neurosurgical and/or neuropharmacological treatments may further improve its therapeutic effectiveness. Finally, other recent reports emphasize that the treatment parameters may be changed in order to approximate clinical/rehabilitation conditions and, nevertheless, remain effective.

5,7-DHT-induced hippocampal 5-HT depletion attenuates behavioural deficits produced by 192 IgG-saporin lesions of septal cholinergic neurons in the rat.

Adult Long-Evans male rats sustained injections of 5,7-dihydroxytryptamine into the fimbria-fornix (2.5 microg/side) and the cingular bundle (1.5 microg/side) and/or to intraseptal injections of 192 IgG-saporin (0.4 microg/side) in order to deprive the hippocampus of its serotonergic and cholinergic innervations, respectively. Sham-operated rats were used as controls. The rats were tested for locomotor activity (postoperative days 18, 42 and 65), spontaneous T-maze alternation (days 20-29), beam-walking sensorimotor (days 34-38), water maze (days 53-64) and radial maze (days 80-133) performances. The cholinergic lesions, which decreased the hippocampal concentration of ACh by about 65%, induced nocturnal hyperlocomotion, reduced T-maze alternation, impaired reference-memory in the water maze and working-memory in the radial maze, but had no effect on beam-walking scores and working-memory in the water maze. The serotonergic lesions, which decreased the serotonergic innervation of the hippocampus by about 55%, failed to induce any behavioural deficit. In the group of rats given combined lesions, all deficits produced by the cholinergic lesions were observed, but the nocturnal hyperlocomotion and the working-memory deficits in the radial maze were attenuated significantly. These results suggest that attenuation of the serotonergic tone in the hippocampus may compensate for some dysfunctions subsequent to the loss of cholinergic hippocampal inputs. This observation is in close concordance with data showing that a reduction of the serotonergic tone, by pharmacological activation of somatodendritic 5-HT(1A) receptors on raphe neurons, attenuates the cognitive disturbances produced by the intrahippocampal infusion of the antimuscarinic drug, scopolamine. This work has been presented previously [Serotonin Club/Brain Research Bulletin conference, Serotonin: From Molecule to the Clinic (satellite to the Society for Neuroscience Meeting, New Orleans, USA, November 2-3, 2000)].

Homotopic septal grafts combined with a hydrogel bridge promote functional recovery in rats with fimbria-fornix lesions: A unit recording study.

Fimbria-fornix lesions abolish the hippocampal electrophysiological activity time-locked to the theta rhythm and alter some functional characteristics of place cells. The present experiment investigated whether homotopic grafts of fetal septal cells can alleviate some of these alter-ations when combined with a polymeric hydrogel bridging a fimbria-fornix lesion-cavity. Eleven months after grafting surgery, unit recordings were obtained from hippocampal neurons of seven rats [two sham-operated (S), two lesion-only (L) and three grafted (G)] while they explored a radial maze. The lesions induced dramatic loss of hippocampal acetylcholinesterase(AChE)-positive reaction products. Surviving grafts were found in the three grafted rats and several AChE-positive processes could be observed in the polymeric hydrogel, as well as in the most dorsal portion of the hippocampal parenchyma. Of 168 recorded units, 132 were hippocampal interneurons (i.e., fired rapidly everywhere in the maze), and 36 were pyramidal place cells (i.e., fired only when the rat was in a specific location in the maze, the place field). The overall firing characteristics of either cell type were similar in S, L and G rats. However, while none of the interneurons recorded from L rats was found to fire rhythmically, a significant proportion of interneurons recorded from S and G rats had an activity pattern time-locked to the theta rhythm [S: 16/19 (84 %); G : 22/70 (31 %)]. In addition, the increase in firing activity observed in interneurons recorded from S rats when they were moving was disrupted in cells from L rats, but partially restored in cells from G rats. Concerning place cells, most (93 %) place fields in S rats were stable relative to extra-maze cues when the radial maze was rotated, while they followed the maze rotation in both L and G rats. Because of the low number of rats used, the present results should be considered with caution. Nevertheless, they indicate graft-induced recovery of some properties of hippocampal function following fimbria-fornix damage, and suggest that homotopic transplants of projection neurons may foster some func-tional recovery when provided with a biomaterial allowing the host or grafted neurons to cross the lesion cavity.